FDA Approves First Breast Cancer Drug to Target PIK3CA Mutation Plus Companion Diagnostic Test

Last week, on the same day that Novartis earned FDA approval for its $2.1 million gene therapy for spinal muscular atrophy, the drug maker also earned a second approval that was overshadowed by the most expensive drug to date.

The FDA approved alpelisib (Piqray), an oral drug to be used in combination with endocrine therapy fulvestrant for the treatment of men and postmenopausal women with hormone receptor (HR-positive), human epidermal growth factor receptor 2 (HER2)-negative, PIK₃CA-mutated, advanced or metastatic breast cancer following disease progression on or after an endocrine-based regimen.

“The approval of Piqray, which was discovered at the Novartis Institutes for BioMedical Research, marks the first ever treatment specifically for HR+/HER2- advanced breast cancer that specifically addresses the needs of the patients living with this mutation,” Susanne Schaffert, PhD, chief executive officer of Novartis Oncology, said in a press release.

The approval was based on the results from the randomized phase 3 SOLAR-1 trial that enrolled 572 postmenopausal women and men. The trial demonstrated that alpelisib plus fulvestrant nearly doubled median progression-free survival (PFS) compared with fulvestrant alone (median PFS 11.0 months versus 5.7 months; HR = 0.65, 95% CI: 0.50=0.85; P <.001).

Additionally, the overall response rate (ORR) more than doubled when alpelisib was added to fulvestrant in patients with a PIK₃CA mutation, with an ORR of 35.7% compared with 16.2% for fulvestrant alone (P = 0.0002).

Common adverse events seen with alpelisib are high blood sugar, increase in creatinine, diarrhea, rash, decrease in lymphocyte count, elevated liver enzymes, nausea, fatigue, low red blood cell count, vomiting, and weight loss, among others.

The drug approval also comes with the approval for its companion diagnostic test, therascreen PIK₃CA RGQ PCR Kit, to detect the PIK₃CA mutation in a tissue and/or liquid biopsy. However, as noted by the FDA, patients who are negative by the therascreen test using the liquid biopsy should undergo a tumor biopsy to test for the PIK₃CA mutation.

“Piqray is the first PI₃K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer. The ability to target treatment to a patient’s specific genetic mutation or biomarker is becoming increasingly common in cancer treatment, and companion diagnostic tests assist oncologists in selecting patients who may benefit from these targeted treatments,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement.

Notably, this was the first novel drug approved under the Real-Time Oncology Review pilot program. This pathway is aimed at streamlining drug reviews while maintaining the quality of the assessment. The program allows for the FDA to begin evaluating key efficacy and safety data sets prior to the official submission of an application, which allows the review team to begin their evaluation and communicate with the applicant earlier.

The drug was also approved using the updated Assessment Aid, which is a multidisciplinary review template intended to focus the FDA’s written review on critical thinking and consistency so as to reduce time spent on administrative tasks.

One of the researchers of the SOLAR-1 trial, Fabrice Andre, MD, PhD, said that the “approval is expected to change the way we practice medicine in advanced breast cancer. For the first time, physicians can test for PIK₃CA biomarkers and develop a treatment plan based on the genomic profile of a patient’s cancer.”